Age-related changes in ploidy levels and biochemical parameters in cardiac myocytes isolated from spontaneously hypertensive rats.

Abstract

Postnatal growth of the mammalian ventricular myocyte is characterized by a brief period of hyperplasia followed by an extensive period of physiological hypertrophy. Using myocytes isolated from both Wistar-Kyoto and spontaneously hypertensive rats from fetus to 10 months old, we analyzed morphological, biochemical, and ploidy changes. Fetal myocytes from both spontaneously hypertensive and Wistar-Kyoto rats were mononuclear, diploid cells. By 4 weeks, adult binucleation levels (84% binuclear) were found, and myocytes pooled from both ventricles demonstrated nuclear ploidy shifts to tetraploid levels. However, analysis of myocytes isolated from left ventricle, right ventricle, and septum showed that nuclear polyploidation was confined to the right ventricle and septum, with few polyploid nuclei detected in the left ventricle. This pattern remained relatively constant through 10 months of age, although spontaneously hypertensive myocytes showed significantly more polyploidation than Wistar-Kyoto in all regions. Biochemical analysis of isolated myocytes substantiated the nuclear ploidy changes and demonstrated elevated protein and ribonucleic acid content in left ventricular myocytes without extensive polyploidation. Since cardiac hypertrophy, both physiological and pathological, is associated primarily with the left ventricle and occurs in the absence of significant ploidy changes, these findings suggest that a unique pattern of gene regulation may be ongoing in the left ventricle myocytes that is not present in the septum and right ventricle. These variations may be essential for cellular hypertrophy under normal and pathological conditions.

Discordant on/off switching of gene expression in myocytes during cardiac hypertrophy in vivo

“…The third population with undetectable levels of expression corresponds to cells with indicator genes off in both nuclei. Previous studies (15) have shown that the vast majority (Ͼ91%) of the adult mouse cardiac myocytes are binucleate, and Engelmannn et al (31) have shown that multinucleate myocytes in the adult rat heart are least frequent in the left ventricle compared with the right ventricle and septum. Because our analyses were done exclusively in the left ventricle of the hearts, the relative contributions of the few mononucleate or multinucleate myocytes that may be present in the left ventricle are unlikely to have a major effect on our overall analyses and conclusions.…”

Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart.

“…In animal experimentation of short-term pressure hypertrophy the myocardial adaptation has been found to consist of cellular enlargement with little or no DNA synthesis in the expanding myocytes (21,22), so that the possibility of nuclear and cellular hyperplasia has been severely questioned. Studies performed in humans, however, have indicated that when the heart is subjected to a prolonged and sustained load, hyperplasia ofmyocyte nuclei occurs (23)(24)(25).…”

Paclitaxel Induces Primary and Postmitotic G1 Arrest in Human Arterial Smooth Muscle Cells

“…Polyploidy is normally seen where cellular hypertrophy occurs with various cell types such as terminally differentiated cardiac myocytes, nonterminally differentiated hepatocytes, and smooth muscle cells. [50][51][52][53] Polyploidy in human artery wall smooth muscle cells ranged from 1 to 7% of the SMC population depending on the age of the subject. 54 While polyploidy can lead to altered gene expression in yeast 55 the functional significance of polyploidy is unknown in SMC.…”